S3134 Metabolic Profile Alterations as Early Indicators of Gastrointestinal Stromal Tumor (GIST) Recurrence and Imatinib Resistance

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract, occurring at a global rate of approximately 10-15 per million per year. Despite surgery and imatinib for high-risk cases, recurrence remains high, with a 5-year rate of 47%, often due to resistance from new kinase mutations. Imatinib affects lipid metabolism in patients with chronic myeloid leukemia and GIST. This study examines metabolic trends in patients with recurrent GIST post-resection on imatinib and proposes that these biomarkers may help guide management in cases of resistance. Methods: In this retrospective cohort study, we analyzed de-identified patient records from the TriNetX database, which aggregates clinical data for more than 170 million patients across 145 healthcare systems in 18 countries. This study examined metabolic biomarkers including total cholesterol, triglycerides (TG), high density lipoprotein cholesterol (HDL-C), TG/HDL ratio, low density lipoprotein cholesterol (LDL-C), hemoglobin A1C, body mass index (BMI) and thyroid-stimulating hormone (TSH). Results: Thirty-six patients were included in this analysis. On average, patients had resection surgery 25.9 months prior to recurrence diagnosis. Total cholesterol and LDL-C were significantly increasing (P < 0.05) with a high positive correlation (correlation coefficient [R] = 0.92; R = 0.87) prior to time of recurrence. HDL-C was found to be significantly decreasing (P < 0.05) with a negative correlation (R = -0.70). BMI was also significantly elevated (P < 0.05) with a negligible correlation (R = -0.03). TG were found to have a significant high positive correlation (P < 0.05; R = 0.93) and TSH was found to have a significant high negative correlation (P = 0.049; R = -0.88). After recurrence was found, patients were started on second- and third-line therapies. Conclusion: This study found that patients who experienced GIST recurrence showed worsening metabolic profiles leading up to the diagnosis of recurrence. Specifically, total cholesterol, LDL, BMI, and TG were trending up while HDL and TSH were trending down. Imatinib has been shown to have significant improvements in lipid and glycemic profiles in patients with GIST. As a result, the worsening of patients’ metabolic parameters leading up to the time of recurrence diagnosis may suggest imatinib resistance and recurrence. Therefore, we posit that these biomarkers can potentially be harnessed as tools for early detection of these events.